A protocol for scoping reviews on the role of whole-body and dedicated body-part magnetic resonance imaging for assessment of adult and juvenile idiopathic inflammatory myopathies.

Currently, standardized magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults are lacking. Therefore, we will perform a scoping review of the literature to collate and evaluate the existing semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs. The aim is to compile evidence-based information that will facilitate the future development of a universal standardized MRI scoring system for both research and clinical applications in IIM. A systematic search of electronic databases (PubMed, EMBASE, and Cochrane) will be undertaken to identify relevant articles published between January 2000 and October 2023. Data will be synthesized narratively. This scoping review seeks to comprehensively summarize and evaluate the evidence on the scanning protocols and scoring systems used in the assessment of diagnosis, disease activity, and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for the MRI assessment of skeletal muscle changes in patients with IIMs.

Metal record of copper-based antifouling paints in sediment core following marina construction and operation.

Marinas are central hubs of global maritime leisure and transport, yet their operations can deteriorate the environmental quality of sediments. In response, this study investigated the metal contamination history associated with antifouling paint uses in a sediment core collected from Bracuhy marina (Southeast Brazil). Analysis target major and trace elements (Cu, Zn, Pb, Cd and Sn), rare earth elements (REEs), and Pb isotopes. The modification in Pb isotopic ratios and REEs pattern unequivocally revealed sediment provenance disruption following the marina construction. Metal distribution in the sediment core demonstrates that concentrations of Cu and Zn increased by up to 15 and 5 times, respectively, compared to the local background. This severe Cu and Zn contamination coincides with the onset of marina operations and can be attributed to the use of antifouling paints.

Spirituality, Religiosity, and Mental Health in Patients with Idiopathic Inflammatory Myopathies: A Brazilian Multicentric Case-Control Study.

No published studies have investigated the correlation between religiosity, spirituality, mental health, and idiopathic inflammatory myopathy (IIM) or systemic autoimmune myopathy. Therefore, we aimed to evaluate the association between religiosity/spirituality, sociodemographic factors, and the mental health of IIM patients. This is a multicenter case-control study that included 151 patients with IIMs and 95 individuals without autoimmune diseases (controls), held between August 2022 and April 2023. This study used a semi-structured questionnaire that included sociodemographic information and the juxtaposition of the following questionnaires: the Attitudes Related to Spirituality Scale (ARES); the Duke University Religion Index (DUKE), which is composed of the organizational religious affiliation (ORA), non-organizational religious affiliation (NORA), and intrinsic religiosity (IR) domains; and the General Health Questionnaire-12 (GHQ-12). Data were analyzed using Epi Info software 7.2.5 (Centers for Disease Control and Prevention, Atlanta, GA, USA). A comparison between the mean values of the ARES, DUKE, and GHQ-12 scales was made using the Wilcoxon-Mann-Whitney and Kruskal-Wallis tests. A logistic regression test was used with the variables whose difference was statistically significant in the univariate analysis. Correlation analysis was performed using the Spearman rho coefficient. A higher prevalence of evangelicals and a lower prevalence of Catholics (p < 0.050) were seen in the IIM group compared to controls. Positive association was demonstrated between IIMs and the pardo ethnicity (OR = 2.26, 95% CI = 1.20-4.25, p = 0.011), highest ORA (OR = 2.81, 95% CI = 1.53-5.15, p < 0.001), NORA (OR = 3.99, 95% CI = 1.94-8·18, p < 0.001), IR (OR = 5.27, 95% CI = 2.32-11.97, p < 0.001), and ARES values (OR = 1.08, 95% CI = 1.04-1.13, p < 0.001). Mental health levels were compared between the groups (p > 0.999). Therefore, higher levels of religiosity and spirituality were observed in the IIM group than in the control group, but there was a similar distribution of mental health levels. The following can be cited as advantages of the present study: (i) the large sample for a rare disease with the presence of a control group; (ii) the multicenter characteristic with participation from three regions of Brazil; (iii) being the first study to map aspects of religiosity, spirituality, and mental health in IIMs.

Genomic analyses of a new baculovirus isolated from the wheat armyworm, Mythimna sequax (Franclemont) (Lepidoptera: Noctuidae).

We report the genomic analysis of a novel alphabaculovirus, Mythimna sequax nucleopolyhedrovirus isolate CNPSo-98 (MyseNPV-CNPSo-98), obtained from cadavers of the winter crop pest, Mythimna sequax Franclemont (Lepidoptera: Noctuidae). The insects were collected from rice fields in Southern Brazil in the 1980's and belongs to the 'EMBRAPA-Soja' Virus Collection. High-throughput sequencing reads of DNA from MyseNPV occlusion bodies and assembly of the data yielded an AT-rich circular genome contig of 148,403 bp in length with 163 annotated opening reading frames (ORFs) and four homologous regions (hrs). Phylogenetic inference based on baculovirus core protein sequence alignments indicated that MyseNPV-CNPSo-98 is a member of Alphabaculovirus genus that clustered with other group II noctuid-infecting baculoviruses, including viruses isolated from Helicoverpa armigera and Mamestra spp. The genomes of the clade share strict collinearity and high pairwise nucleotide identity, with a common set of 149 genes, evolving under negative selection, except a bro gene. Branch lengths and Kimura-2-parameter pairwise nucleotide distances indicated that MyseNPV-CNPSo-98 represents a distinct lineage that may not be classified in any of the currently listed species in the genus.

Schwann cell TRPA1 elicits reserpine-induced fibromyalgia pain in mice.

BACKGROUND AND PURPOSE: Fibromyalgia is a complex clinical disorder with an unknown aetiology, characterized by generalized pain and co-morbid symptoms such as anxiety and depression. An imbalance of oxidants and antioxidants is proposed to play a pivotal role in the pathogenesis of fibromyalgia symptoms. However, the precise mechanisms by which oxidative stress contributes to fibromyalgia-induced pain remain unclear. The transient receptor potential ankyrin 1 (TRPA1) channel, known as both a pain sensor and an oxidative stress sensor, has been implicated in various painful conditions. EXPERIMENTAL APPROACH: The feed-forward mechanism that implicates reactive oxygen species (ROS) driven by TRPA1 was investigated in a reserpine-induced fibromyalgia model in C57BL/6J mice employing pharmacological interventions and genetic approaches. KEY RESULTS: Reserpine-treated mice developed pain-like behaviours (mechanical/cold hypersensitivity) and early anxiety-depressive-like disorders, accompanied by increased levels of oxidative stress markers in the sciatic nerve tissues. These effects were not observed upon pharmacological blockade or global genetic deletion of the TRPA1 channel and macrophage depletion. Furthermore, we demonstrated that selective silencing of TRPA1 in Schwann cells reduced reserpine-induced neuroinflammation (NADPH oxidase 1-dependent ROS generation and macrophage increase in the sciatic nerve) and attenuated fibromyalgia-like behaviours. CONCLUSION AND IMPLICATIONS: Activated Schwann cells expressing TRPA1 promote an intracellular pathway culminating in the release of ROS and recruitment of macrophages in the mouse sciatic nerve. These cellular and molecular events sustain mechanical and cold hypersensitivity in the reserpine-evoked fibromyalgia model. Targeting TRPA1 channels on Schwann cells could offer a novel therapeutic approach for managing fibromyalgia-related behaviours.

Spatiotemporal and multi-isotope assessment of metal sedimentation in the Great Lakes.

This study investigates spatiotemporal dynamics in metal sedimentation in the North American Great Lakes and their underlying biogeochemical controls. Bulk geochemical and isotope analyses of n = 72 surface and core sediment samples show that metal (Cu, Zn, Pb) concentrations and their isotopic compositions vary spatially across oligotrophic to mesotrophic settings, with intra-lake heterogeneity being similar or higher than inter-lake (basin-scale) variability. Concentrations of Cu, Zn, and Pb in sediments from Lake Huron and Lake Erie vary from 5 to 73 mg/kg, 18-580 mg/kg, and 5-168 mg/kg, respectively, but metal enrichment factors were small (<2) across the surface- and core sediments. The isotopic signatures of surface sediment Cu (δ65Cu between -1.19‰ and +0.96‰), Zn (δ66Zn between -0.09‰ and +0.41‰) and Pb (206/207Pb from 1.200 to 1.263) indicate predominantly lithogenic metal sourcing. In addition, temporal trends in sediment cores from Lake Huron and Lake Erie show uniform metal concentrations, minor enrichment, and Zn and Pb isotopic signatures suggestive of negligible in-lake biogeochemical fractionation. In contrast, Cu isotopic signatures and correlation to chlorophyll and macronutrient levels suggest more differentiation from source variability and/or redox-dependent fractionation, likely related to biological scavenging. Our results are used to derive baseline metal sedimentation fluxes and will help optimize water quality management and strategies for reducing metal loads and enrichment in the Great Lakes and beyond.

The long-term effect on functional outcome of endoscopic brainwashing for intraventricular hemorrhage compared to external ventricular drainage alone: A retrospective single-center cohort study.

Background: Intraventricular hemorrhage (IVH) is a complex condition with both mechanical and chemical effects, resulting in mortality rates of 50-80%. Recent reports advocate for neuroendoscopic treatment, particularly endoscopic brainwashing (EBW), but long-term functional outcomes remain insufficiently explored. This study aims to outline the step-by-step procedure of EBW as applied in our institution, providing results and comparing them with those of external ventricular drainage (EVD) alone. Methods: We performed a retrospective analysis of adult patients with IVH who underwent EBW and patients submitted to EVD alone at our institution. All medical records were reviewed to describe clinical and radiological characteristics. Results: Although both groups had similar baseline factors, EBW patients exhibited a larger hemoventricle (median Graeb score 25 vs. 23 in EVD, P = 0.03) and a higher prevalence of chronic kidney disease and diabetes. Short-term mortality was lower in EBW (52% and 60% at 1 and 6 months) compared to EVD (80% for both), though not statistically significant (P = 0.06). At one month, 16% of EBW patients achieved a good outcome (Modified Rankin scale < 3) versus none in the EVD group (P = 0.1). In the long term, favorable outcomes were observed in 32% of EBW patients and 11% of EVD patients (P = 0.03), with no significant difference in shunt dependency. Conclusion: Comparing EBW and EVD, patients submitted to the former treatment have the highest modified Graeb scores and, at a long-term follow-up, have better outcomes, demonstrated by the improvement of the patients in the follow-up.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.

The multispecies stinkbug iflavirus Halyomorpha halys virus detected in the multispecies stinkbug egg parasitoid microwasp, Telenomus podisi (Ashmead) (Hymenoptera: Platygastridae).

Wasps are important parasitoids of stinkbugs and frequently exposed to various types of microorganisms through environmental contact and fecal-oral transmission route. Many parasitize stinkbug eggs and are commercially used in the field to control insect population. The parasitoid T. podisi is known for its high parasitism capacity and ability to target multiple species of stinkbugs. In this study we asked whether T. podisi exposed to eggs infected by a multispecies asymptomatic stinkbug virus, the Halyomorpha halys virus (HhV) would get infected. HhV is a geographically distributed multispecies iflavirus previously found to infect four stinkbug hosts, including three Brazilian species, Chinavia ubica, Euschistus heros and Diceraeus melacanthus, and T. posidi can parasitize all of them. As results, RT-PCR screening revealed positive samples for the HhV genome in two out of four tested pools of T. podisi, whereas the antigenome, indicative of replicative activity, was not detected. The wasps were raised in E. heros eggs that presented both the genome and the antigenome forms of the HhV genome. Subsequent RNA-deep sequencing of HhV positive T. podisi RNA pools yielded a complete genome of HhV with high coverage. Phylogenetic analysis positioned the isolate HhV-Tp (isolate Telenomus podisi) alongside with the stinkbug HhV. Analysis of transcriptomes from several hymenopteran species revealed HhV-Tp reads in four species. However, the transmission mechanism and the ecological significance of HhV remain elusive, warranting further studies to illuminate both the transmission process and its capacity for environmental propagation using T. podisi as a potential vector.

Seasonal and multi-decadal zinc isotope variations in blue mussels from two sites with contrasting zinc contamination levels.

Zinc (Zn) isotope compositions in soft mussel tissues help identify internal biological processes and track coastal Zn sources in coastal environments, thus aiding in managing marine metal pollution. This study investigated the seasonal and multi-decadal Zn isotope compositions of blue mussels (genus Mytilus) from two French coastal sites with contrasting Zn environmental contamination. Concurrently, we characterized the isotope ratios of sediments and plankton samples at each site to understand the associations between organisms and abiotic compartments. Our primary objective was to determine whether these isotope compositions trace long-term anthropogenic emission patterns or if they reflect short-term biological processes. The multi-decadal isotope profiles of mussels in the Loire Estuary and Toulon Bay showed no isotope variations, implying the enduring stability of the relative contributions of natural and anthropogenic Zn sources over time. At seasonal scales, Zn isotope ratios were also constant; hence, isotope effects related to spawning and body growth were not discernible. The multi-compartmental analysis between the sites revealed that Toulon Bay exhibits a remarkably lower Zn isotope ratio across all studied matrices, suggesting the upward transfer of anthropogenic Zn in the food web. In contrast, the Zn isotope variability observed for sediments and organisms from the Loire Estuary fell within the natural baseline of this element. In both sites, adsorptive geogenic material carrying significant amounts of Zn masks the biological isotope signature of plankton, making it difficult to determine whether the Zn isotope ratio in mussels solely reflects the planktonic diet or if it is further modified by biological homeostasis. In summary, Zn isotope ratios in mussels offer promising avenues for delineating source-specific isotope signatures, contingent upon a comprehensive understanding of the isotope fractionation processes associated with the trophic transfer of this element through the plankton.

PRE1BRAZIL Protocol: A Randomized Controlled Trial to Evaluate the Effectiveness and Safety of the DPP-4 Inhibitor Alogliptin in Delaying the Progression of Stage 2 Type 1 Diabetes.

Background: The incidence of Type 1 Diabetes Mellitus (T1DM) is on the rise. Since there is no curative treatment, it is urgent to look for therapies that can delay disease progression and protect pancreatic ß-cells. Dipeptidyl peptidase-4 inhibitors (DPP-4i) have shown potential in modulating inflammation and preventing ß-cell destruction. This protocol describes an upcoming trial to evaluate the effectiveness of the DPP-4i alogliptin in delaying the progression of stage 2 (presymptomatic) to stage 3 (symptomatic) T1DM. Patients and Methods: We propose a two-year, two-arm, multicenter, randomized, open-label clinical trial targeting Brazilian patients aged 18 to 35 with stage 2 T1DM. The study, facilitated by the custom-developed "PRE1BRAZIL" web application, aims to enroll 130 participants. They will be randomly assigned in a 1:1 ratio to either a treatment group (alogliptin 25 mg daily plus regular clinical and laboratory assessments) or a control group (regular assessments only). The primary outcome is the rate of progression to stage 3 T1DM. Secondary outcomes include changes in A1c levels, glucose levels during a 2-hour oral glucose tolerance test (OGTT), C-peptide levels, exogenous insulin requirements, Insulin-Dose Adjusted A1c (IDAA1c), and the incidence of diabetic ketoacidosis (DKA) in those advancing to stage 3. Discussion: This protocol outlines the first randomized clinical trial (RCT) to investigate the impact of a DPP-4i in the presymptomatic stage of T1DM. The trial is designed to provide critical insights into the role of DPP-4i in the secondary prevention of T1DM. Utilizing the "PRE1BRAZIL" web application is expected to enhance participant enrollment and reduce operational costs. Registration: Brazilian Registry of Clinical Trials.

Copper and zinc isotope systematics in different bivalve mollusk species from the French coastline: Implications for biomonitoring.

Zinc (Zn) and copper (Cu) stable isotopic compositions have been analyzed in various species of bivalve mollusks worldwide, but no comprehensive systematic interspecies comparison exists. Thus, we assessed isotope differences between species harvested in emblematic French coastal ecosystems to unveil biologically driven Cu and Zn isotope fractionation patterns. Inter-species isotopic variability of Cu is larger than Zn, with organisms that regulate internal concentrations displaying preferential bioaccumulation of heavy isotopes. The degree of internal isotope fractionation decreases from mussels > clams > oysters, affecting Cu more than Zn. The less pronounced Zn inter-specie variability helps preserve source information more reliably. Spatial analysis of a single oyster species denotes thus an important isotope variability of environmental Zn sources, including natural, anthropogenic and dietary components. Overall, results highlight the importance of considering systematic offset in Cu and Zn isotope values when comparing data from different bivalve species.

Laser Engineering Nanocarbon Phases within Diamond for Science and Electronics.

Diamond, as the densest allotrope of carbon, displays a range of exemplary material properties that are attractive from a device perspective. Despite diamond displaying high carbon-carbon bond strength, ultrashort (femtosecond) pulse laser radiation can provide sufficient energy for highly localized internal breakdown of the diamond lattice. The less-dense carbon structures generated on lattice breakdown are subject to significant pressure from the surrounding diamond matrix, leading to highly unusual formation conditions. By tailoring the laser dose delivered to the diamond, it is shown that it is possible to create continuously modified internal tracks with varying electrical conduction properties. In addition to the widely reported conducting tracks, conditions leading to semiconducting and insulating written tracks have been identified. High-resolution transmission electron microscopy (HRTEM) is used to visualize the structural transformations taking place and provide insight into the different conduction regimes. The HRTEM reveals a highly diverse range of nanocarbon structures are generated by the laser irradiation, including many signatures for different so-called diaphite complexes, which have been seen in meteorite samples and seem to mediate the laser-induced breakdown of the diamond. This work offers insight into possible formation methods for the diamond and related nanocarbon phases found in meteorites.

Does the Impact of COVID-19 on Patients With Systemic Sclerosis Change Over Time?

OBJECTIVE: The outcome of patients with COVID-19 improved over the pandemic, including patients with systemic rheumatic diseases. However, data on patients with systemic sclerosis (SSc) are lacking. This study aimed to assess the outcome of patients with both SSc and COVID-19 over several waves. METHODS: Patients with both SSc and COVID-19 who were registered in the European Scleroderma Trials and Research group (EUSTAR) were collected between April 2020 and April 2021. Patients were assigned to waves 1, 2, or 3 depending on the date of their COVID-19 diagnosis. Primary endpoints were death, intensive care unit stay, or ventilatory support (severe outcome). Subgroup analyses of patients who were hospitalized or died were conducted. General and SSc-specific characteristics and treatment were compared over the waves. Descriptive statistics and multivariate logistic regression were applied. RESULTS: A total of 333 patients were included; 57 patients (17%) had a severe outcome, and 30 patients (9%) died. Compared to wave 1, significantly fewer patients with SSc suffered from severe COVID-19 in waves 2 and 3 (28.2% vs 9.8% and 12.7%; P < 0.001), fewer patients required hospitalization (46.7% vs 19.6% and 25.5%; P < 0.001) or ventilatory support (24.0% vs 8.7% and 10.9%; P = 0.001), and fewer patients died (15.7% vs 5.0% and 7.5%; P = 0.011). Patients were significantly younger, more often men, had less frequent arterial hypertension, and less SSc cardiac involvement over waves 1 to 3. Patients received significantly less medium to high doses of corticosteroids as they did SSc treatment. CONCLUSION: The outcome of patients with both SSc and COVID-19 improved significantly over time because of intrinsic and extrinsic factors.

The French Mussel Watch Program reveals the attenuation of coastal lead contamination over four decades.

The mid-20th century industrial peak caused severe global lead (Pb) marine contamination. Although Europe initiated Pb emission reduction regulations in the 1980s, the short- and long-term impacts remain unclear. This study investigates the evolution of Pb contamination on the French coast through elemental and isotope analysis in oysters and mussels from the French "Mussel Watch" Program. Observations at 114 monitoring stations over four decades have shown decreasing Pb levels in these bivalve mollusks. In 1988, 95 % exceeded the background reference values; this level had dropped to 39 % by 2021. The Pb isotope ratios in bivalves from eight target sites revealed a reduction in bioaccumulated anthropogenic Pb, albeit without complete elimination. The long residence time of legacy Pb combined with inputs from diffuse urban sources likely explains the persistent presence of anthropogenic Pb on the French coast. This study endorses the importance of continuous biomonitoring to evaluate environmental regulations and policies.

Human CD79b+ neutrophils in the blood are associated with early-stage melanoma.

Purpose: Due to their abundance in the blood, low RNA content, and short lifespan, neutrophils have been classically considered to be one homogenous pool. However, recent work has found that mature neutrophils and neutrophil progenitors are composed of unique subsets exhibiting context-dependent functions. In this study, we ask if neutrophil heterogeneity is associated with melanoma incidence and/or disease stage. Experimental design: Using mass cytometry, we profiled melanoma patient blood for unique cell surface markers among neutrophils. Markers were tested for their predictiveness using flow cytometry data and random forest machine learning. Results: We identified CD79b+ neutrophils (CD3-CD56-CD19-Siglec8-CD203c-CD86LoCD66b+CD79b+) that are normally restricted to the bone marrow in healthy humans but appear in the blood of subjects with early-stage melanoma. Further, we found CD79b+ neutrophils present in tumors of subjects with head and neck cancer. AI-mediated machine learning analysis of neutrophils from subjects with melanoma confirmed that CD79b expression among peripheral blood neutrophils is highly important in identifying melanoma incidence. We noted that CD79b+ neutrophils possessed a neutrophilic appearance but have transcriptional and surface-marker phenotypes reminiscent of B cells. Compared to remaining blood neutrophils, CD79b+ neutrophils are primed for NETosis, express higher levels of antigen presentation-related proteins, and have an increased capacity for phagocytosis. Conclusion: Our work suggests that CD79b+ neutrophils are associated with early-stage melanoma.

Multivariate adaptive shrinkage improves cross-population transcriptome prediction and association studies in underrepresented populations.

Transcriptome prediction models built with data from European-descent individuals are less accurate when applied to different populations because of differences in linkage disequilibrium patterns and allele frequencies. We hypothesized that methods that leverage shared regulatory effects across different conditions, in this case, across different populations, may improve cross-population transcriptome prediction. To test this hypothesis, we made transcriptome prediction models for use in transcriptome-wide association studies (TWASs) using different methods (elastic net, joint-tissue imputation [JTI], matrix expression quantitative trait loci [Matrix eQTL], multivariate adaptive shrinkage in R [MASHR], and transcriptome-integrated genetic association resource [TIGAR]) and tested their out-of-sample transcriptome prediction accuracy in population-matched and cross-population scenarios. Additionally, to evaluate model applicability in TWASs, we integrated publicly available multiethnic genome-wide association study (GWAS) summary statistics from the Population Architecture using Genomics and Epidemiology (PAGE) study and Pan-ancestry genetic analysis of the UK Biobank (PanUKBB) with our developed transcriptome prediction models. In regard to transcriptome prediction accuracy, MASHR models performed better or the same as other methods in both population-matched and cross-population transcriptome predictions. Furthermore, in multiethnic TWASs, MASHR models yielded more discoveries that replicate in both PAGE and PanUKBB across all methods analyzed, including loci previously mapped in GWASs and loci previously not found in GWASs. Overall, our study demonstrates the importance of using methods that benefit from different populations' effect size estimates in order to improve TWASs for multiethnic or underrepresented populations.

TRP Channels in Cancer: Signaling Mechanisms and Translational Approaches.

Ion channels play a crucial role in a wide range of biological processes, including cell cycle regulation and cancer progression. In particular, the transient receptor potential (TRP) family of channels has emerged as a promising therapeutic target due to its involvement in several stages of cancer development and dissemination. TRP channels are expressed in a large variety of cells and tissues, and by increasing cation intracellular concentration, they monitor mechanical, thermal, and chemical stimuli under physiological and pathological conditions. Some members of the TRP superfamily, namely vanilloid (TRPV), canonical (TRPC), melastatin (TRPM), and ankyrin (TRPA), have been investigated in different types of cancer, including breast, prostate, lung, and colorectal cancer. TRP channels are involved in processes such as cell proliferation, migration, invasion, angiogenesis, and drug resistance, all related to cancer progression. Some TRP channels have been mechanistically associated with the signaling of cancer pain. Understanding the cellular and molecular mechanisms by which TRP channels influence cancer provides new opportunities for the development of targeted therapeutic strategies. Selective inhibitors of TRP channels are under initial scrutiny in experimental animals as potential anti-cancer agents. In-depth knowledge of these channels and their regulatory mechanisms may lead to new therapeutic strategies for cancer treatment, providing new perspectives for the development of effective targeted therapies.

Linking multivariate statistical methods and water quality indices to evaluate the natural and anthropogenic geochemical processes controlling the water quality of a tropical watershed.

The improvement of water management requires monitoring techniques that accurately evaluate water quality status and detect the effects of land use changes on water chemistry. This study aimed to evaluate how multivariate statistical methods and water quality indices can be applied together to evaluate the processes controlling water chemical composition and the overall water quality status of a tropical watershed. Thirty-four water samples were collected in the Formoso River basin, located on the border of the Amazon Forest. Water parameters were measured in situ using a multiparameter and in the lab using spectroscopic and volumetric techniques. The water quality dataset was interpreted through principal component analysis, multivariate linear regression, and water quality indices. Statistical methods allowed us to identify the sources and geochemical processes controlling water quality chemistry, which were carbonate dissolution, runoff/erosion, nutrient input due to anthropogenic activities, and redox reactions in flooded zones. They were also used to create linear functions to evaluate the effects of land use changes on the geochemical processes controlling water chemistry. Conversely, the water quality indices provide information about the overall condition of the water. The Weight-Arithmetic Quality Index correctly evaluates water suitability for its multiple uses, according to the Brazilian guidelines. Conversely, the Ontario Water Quality Index is not suitable to evaluate the water quality of tropical rivers, since the usual higher water temperature and the low oxygen contents associated with tropical environments result in biased water quality evaluations by this index.